The rationale for the design of control groups in tuina clinical trial is the foundation for rigorously validating the effectiveness and safety of this therapy. This article reviewed the current state of the design of tuina placebo in control groups of clinical trials， pointed out the necessity of setting up tuina placebo in clinical trials of tuina， analyzed the challenges in implementing blinding of tuina manipulation， and concluded that tuina placebo is still challenged by the placebo effect， the diversification of tuina manipulation but the lack of standardization， and the difficulty of implementing blinding due to the high level of public awareness of tuina. This article also summarized the design of placebo manipulation in three types of clinical trials， including spinal manipulation， acupressure， and paediatric tuina， and proposed four strategies for designing placebo tuina manipulation-controlling placebo effects， developing operational standards for placebo tuina manipulation， ensuring the rigor of blinding implementation， and applying new technologies to enhance the standardization and blinding capacity of placebo tuina methods. So the article is aimed at improving the methodological quality of tuina clinical trial designs， and promoting the standardization and scientificity of tuina clinical trial design.

Objective:To evaluate the predictive value of the Controlling Nutritional Status (CONUT) score for severe acute pancreatitis (SAP).Methods:A total of 426 patients with acute pancreatitis (AP) admitted to the First Affiliated Hospital of Zhengzhou University between January and December 2024 were retrospectively reviewed. After applying exclusion criteria, 189 patients were included and classified into non-severe AP (NSAP) and SAP groups according to diagnostic criteria. Demographic characteristics (age, sex, underlying diseases), vital signs, CONUT score, Bedside Index for Severity in Acute Pancreatitis (BISAP) score, and laboratory parameters (including complete blood count, blood glucose, liver and kidney function, coagulation profile, amylase, and lipase) on admission were compared between the two groups. Binary logistic regression was used to identify independent risk factors associated with AP severity. Receiver operating characteristic (ROC) curves were generated to assess the predictive performance of each indicator by determining the area under the curve (AUC), sensitivity, specificity, and optimal cutoff values.Results:Compared with the NSAP group, the SAP group had significantly longer hospital stays, higher respiratory rates, and elevated levels of PCT, CRP, absolute neutrophil count, AST, GGT, PT, D-dimer, INR, fibrinogen, FDP, as well as higher CONUT, SIRS, and BISAP scores (all P < 0.05). In contrast, the NSAP group showed significantly higher red blood cell count, hemoglobin, absolute lymphocyte count, serum calcium, albumin, total cholesterol, prothrombin time activity, and PNI score (all P < 0.05). Binary logistic regression analysis identified CONUT score ( OR = 1.623, 95% CI: 1.048–2.512) and BISAP score ( OR = 19.608, 95% CI: 6.585–58.387) as independent risk factors for disease severity. The AUC values for predicting SAP using CONUT score, BISAP score, and their combination were 0.694, 0.815, and 0.864, respectively. Conclusions:The CONUT score is an early independent risk factor for SAP. Combining CONUT with BISAP scores provides better predictive performance for assessing the severity of acute pancreatitis.

As a biocatalyst, laccase has been widely studied and applied in the papermaking industry. However, the low catalytic efficiency and poor stability of natural laccase limit its application in the pulping process. To develop the laccase with high activity and strong tolerance, we carried out directed evolution for modification of the laccase derived from Bacillus pumilus and screened out the mutants F282L/F306L and Q275P from the random mutant library by high-throughput screening. The specific activities of F282L/F306L and Q275P were 280.87 U/mg and 453.94 U/mg, respectively, which were 1.42 times and 2.30 times that of the wild-type laccase. Q275P demonstrated significantly improved thermal stability, with the relative activity 20% higher than that of the wild-type laccase after incubation at 40 ℃, 50 ℃, and 70 ℃ for 4 h. F282L/F306L and Q275P showed greater tolerance to metal ions and organic solvents than the wild-type laccase. The K_m value of the wild-type laccase was 374.97 μmo/L, and those of F282L/F306L and Q275P were reduced to 318.96 μmo/L and 360.71 μmo/L, respectively, which suggested that the substrate affinity of laccase was improved after mutation. The k_cat values of F282L/F306L and Q275P for the substrate ABTS were 574.00 s^-1 and 898.03 s^-1, respectively, which were 1.1 times and 1.7 times that of the wild-type laccase, indicating the improved catalytic efficiency. Q275P demonstrated better performance than the wild-type laccase in pulping, as manifested by the reduction of 0.82 in the Kappa number and the increases of 2.00% ISO, 7.8%, and 7.2% in whiteness, tensile index, and breaking length, respectively. This work lays a foundation for improving the adaptation of laccase to the environment of the papermaking industry.
Laccase/chemistry* ; Directed Molecular Evolution ; Enzyme Stability ; Bacillus pumilus/genetics* ; Mutation ; Biocatalysis ; Catalysis

Objective:To explore the level of unmet need during chemotherapy for gastric cancer patients, analyze its dynamic trajectory and impact on the economic toxicity of chemotherapy.Methods:Convenience sampling was used to select 385 gastric cancer patients who received chemotherapy from June 2022 to December 2023 at the First Affiliated Hospital of Zhengzhou University. The level of unmet need for patients' first chemotherapy cycle (C 1) , second chemotherapy cycle (C 2) and third chemotherapy cycle (C 3) and economic toxicity at the end of chemotherapy were investigated separately. The latent class growth model (LCGM) was used to analyze classes of unmet need trajectories and to compare differences in patient economic toxicity across classes. Results:Finally 368 patients completed all data collection, and the effective response rate of survey respondents was 95.58%. As chemotherapy progressed, patients' unmet need scores gradually increased, and the unmet need scores of C 1, C 2, and C 3 were (35.54±5.44) , (47.32±6.45) , and (58.19±11.81) , respectively, which were categorized into three latent classes of medium-low level rapid increase group, medium level gradual increase group, and medium level stable group. There were 122 cases (33.15%) in medium-low level rapid increase group, 167 cases (45.38%) in medium level gradual increase group, and 79 cases (21.47%) in medium level stable group. The lowest economic toxicity score was found in medium-low level rapid increase group, followed by medium level gradual increase group, and the highest in medium level stable group, and the difference in economic toxicity scores among the three groups was statistically significant ( P<0.05) . The percentage of patients with positive economic toxicity in the three groups was 45.90% (56/122) , 28.14% (47/167) , and 18.99% (15/79) , respectively, with a statistically significant difference ( P<0.05) . Conclusions:Unmet needs of patients during chemotherapy for gastric cancer show a moderate to high level and gradually increase with the course of chemotherapy. The trajectory can be divided into three latent classes of medium-low level rapid increase group, medium level gradual increase group, and medium level stable group. There are differences in economic toxicity for patients with different classes of unmet need trajectories, with patients in increase or rapid increase groups facing severe economic toxicity.

Objective:To explore the level of unmet need during chemotherapy for gastric cancer patients, analyze its dynamic trajectory and impact on the economic toxicity of chemotherapy.Methods:Convenience sampling was used to select 385 gastric cancer patients who received chemotherapy from June 2022 to December 2023 at the First Affiliated Hospital of Zhengzhou University. The level of unmet need for patients' first chemotherapy cycle (C 1) , second chemotherapy cycle (C 2) and third chemotherapy cycle (C 3) and economic toxicity at the end of chemotherapy were investigated separately. The latent class growth model (LCGM) was used to analyze classes of unmet need trajectories and to compare differences in patient economic toxicity across classes. Results:Finally 368 patients completed all data collection, and the effective response rate of survey respondents was 95.58%. As chemotherapy progressed, patients' unmet need scores gradually increased, and the unmet need scores of C 1, C 2, and C 3 were (35.54±5.44) , (47.32±6.45) , and (58.19±11.81) , respectively, which were categorized into three latent classes of medium-low level rapid increase group, medium level gradual increase group, and medium level stable group. There were 122 cases (33.15%) in medium-low level rapid increase group, 167 cases (45.38%) in medium level gradual increase group, and 79 cases (21.47%) in medium level stable group. The lowest economic toxicity score was found in medium-low level rapid increase group, followed by medium level gradual increase group, and the highest in medium level stable group, and the difference in economic toxicity scores among the three groups was statistically significant ( P<0.05) . The percentage of patients with positive economic toxicity in the three groups was 45.90% (56/122) , 28.14% (47/167) , and 18.99% (15/79) , respectively, with a statistically significant difference ( P<0.05) . Conclusions:Unmet needs of patients during chemotherapy for gastric cancer show a moderate to high level and gradually increase with the course of chemotherapy. The trajectory can be divided into three latent classes of medium-low level rapid increase group, medium level gradual increase group, and medium level stable group. There are differences in economic toxicity for patients with different classes of unmet need trajectories, with patients in increase or rapid increase groups facing severe economic toxicity.

Purpose/Significance The paper studies the co-fund patterns and effectiveness of research fund from the perspective of organization types,and provides theoretical reference for improving medical research funding system in China.Method/Process It takes the field of cervical cancer research as an example,dividing research funds into 5 types:government funds,academic funds,enterprise funds,medical institution funds,and social organization funds.The effectiveness of co-funding is studied based on journal impact index(JII),annual citation index(ACI),annual usage index(AUI)and comprehensive effectiveness score,and pattern recognition and a-nalysis are carried out based on the indicator results.Result/Conclusion The comprehensive effectiveness score of co-funding by univer-sities,enterprises,and social organizations is the highest.Research funding in the medical field can be based on specific research goals and combined multiple funds to achieve overlapping effects and improving the effectiveness of output results.

ObjectiveTo analyze the traditional Chinese medicine （TCM） patterns in patients with spasmodic torticollis and provide reference for standardized differentiation and clinical treatment. MethodsA cross-sectional study was conducted in the spasmodic torticollis outpatient clinic and dystonia ward of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from June 2022 to December 2023. The general information including gender， age， duration of disease and type， and the TCM four examinations data such as symptoms， tongue manifestation and pulse manifestation of 198 patients with spasmodic torticollis were obtained by means of on-site questionnaires. Descriptive frequency analysis， factor analysis， and cluster analysis were performed， and the distribution of major TCM patterns were summarized based on the clinical information. ResultsA total of 198 patients with spasmodic torticollis were included， of which 89 （44.95%） were male and 109 （55.05%） were female， with an average age of 40.70±0.96 years and an average course of disease of 24.78±2.32 months. A total of 296 symptoms/signs were obtained， with a cumulative frequency of 6756 times， of which 58 symptoms/signs had a frequency ≥20%， and the top three were neck and back stiffness （83.84%）， condition related to emotions （74.75%） and irritability （72.73%）. Factor analysis of 58 symptoms/signs showed that factor rotation converged after 51 iterations， resulting in 20 common factors with a cumulative contribution of 64.03%. The top three syndrome elements related to the location of the disease were liver， channels， tendons and bones， and those related nature of the disease were dominated by qi stagnation， blood stasis and yin deficiency. The cluster analysis of the 20 common factors showed that the main TCM patterns were internal stirring of liver wind syndrome， liver-kidney yin deficiency syndrome， turbid phlegm obstruction syndrome， and pathogen congested in the channels syndrome. Among the 198 patients， 81 were diagnosed with internal stirring of liver wind syndrome， 60 with liver-kidney yin deficiency syndrome， 37 with turbid phlegm obstruction syndrome， and 20 with pathogen congested in the channels syndrome.There was no statistically significant difference in the distribution of TCM patterns among patients of different genders， age groups， and duration of disease （P＞0.05）. ConclusionSpasmodic torticollis is mainly located in the liver， mostly with internal stirring of liver wind syndrome， liver-kidney yin deficiency syndrome， turbid phlegm obstruction syndrome， and pathogen congested in the channels syndrome.

Objective To compare biomechanical characteristics of external fixator, Kirschner’s wire, elastic stable intramedullary nailing (ESIN) for fixing proximal humeral fractures in children by finite element method.Methods The CT scanning data from the healthy humerus of an 8-year-old patient with proximal humeralfractures were collected, and the image data were imported in Mimics 21. 0 to establish the rough humeralmodel, which was imported in Geomagic 2013 to construct the three-dimensional (3D) model of cancellous and cortical bones of the humerus. After the model was assembled with 3 fixators ( external fixator, Kirschner’swire, ESIN), it was imported in ANSYS 2019 to simulate the upper limb under quiet, abduction, adduction, flexion, extension, external rotation, internal rotation working conditions. The maximum displacement of the distal humerus, the maximum stress of the fixture, and the maximum displacement of the distal fracture surface were analyzed. Results The minimum values of the maximum displacement of the distal humerus in models fixed by external fixator, Kirschner’s wire, ESIN appeared under extension (2. 406 mm), external rotation (0. 203 mm), external rotation (0. 185 mm) working conditions, respectively. Conclusions External fixator is the most unstable fixation of proximal humeral fractures in children, and the biomechanical performance of ESIN is better than that of external fixator and Kirschner’s wire fixation

Objective:To analyze the rules and distribution of acupuncture points used in pediatric tuina treatment for autumn diarrhea, and to provide a theoretical basis for the promotion and application of Tuina treatment techniques for pediatric diarrhea.Methods:We searched the literature on Tuina treatment of pediatric autumn diarrhea in the Chinese academic journals full-text database (CNKI), Chinese science and technology journals full-text database (VIP), Wanfang database and Chinese biomedical database (SinoMed), and collected the Tuina prescriptions on children's autumn diarrhea disease from the database to March 2021,with the help of the Traditional Chinese Medicine Inheritance Support Platform (V 2.0) software,and Data mining technology was applied to analyze the common acupoints and acupoint distribution of pediatric Tuina treatment of autumn diarrhea to form the core acupoints used in pediatric Tuina treatment of autumn diarrhea.Results:A total of 101 pediatric autumn diarrhea Tuina prescriptions were screened, involving 61 acupoints, among them 18 acupoints used more frequently, and 35 acupoint combinations were obtained, including 15 two-acupoint combinations, 11 three-acupoint combinations, and 2 four-acupoint combinations, and 7 new acupoint combinations were obtained.Conclusion:The core points mainly belong to the spleen meridian, large intestine meridian, abdomen, seven knotted bones, turtle tail, spine, and umbilicus, which can be used as a basic Tuina prescription for clinical reference.

Objective:To investigate and evaluate if pulse oxygen saturation/fraction of inhaled oxygen (SpO 2/FiO 2) can be used, as replacement of arterial partial pressure of oxygen/fraction of inhaled oxygen (PaO 2/FiO 2), to assess oxygenation in acute respiratory distress syndrome (ARDS) patients at different high altitudes in Yunnan Province, and to find a rapid and non-invasive method for the diagnosis of ARDS at different altitudes. Methods:Patients with ARDS at different high altitudes in Yunnan Province from January 2019 to December 2020 were enrolled. The patients were divided into three groups according to different altitudes, and received different oxygen therapies according to their respective medical conditions. Group 1 consisted of patients with moderate to severe ARDS from the department of critical care medicine of the First Affiliated Hospital of Kunming Medical University (average altitude approximately 1 800 m), and received mechanical ventilation to maintain SpO 2 of 0.90-0.96 with a low FiO 2 for more than 30 minutes, and SpO 2, FiO 2, PaO 2 were recorded. Group 2 consisted of patients with moderate to severe ARDS at the department of critical care medicine of People's Hospital of Diqing Tibetan Autonomous Prefecture (mean altitude about 3 200 m), and received oxygen with an attached reservoir mask to maintain SpO 2 of 0.90-0.96 for 10 minutes, and then SpO 2, FiO 2, and PaO 2 were recorded. Group 3 consisted of patients with mild to moderate-severe ARDS who admitted to the emergency department of the People's Hospital of Lijiang (average altitude approximately 2 200 m); when SpO 2 < 0.90, patients received oxygen with the oxygen storage mask, and the FiO 2 required to maintain SpO 2 ≥ 0.90 was recorded, and SpO 2, FiO 2, PaO 2 were recorded after oxygen inhalation for 10 minutes. Spearman coefficient was used to analyze the correlation between SpO 2/FiO 2 and PaO 2/FiO 2 in each group. Linear analysis was used to derive the linear equation between SpO 2/FiO 2 and PaO 2/FiO 2, and to evaluate arterial pH, arterial partial pressure of carbon dioxide (PaCO 2), FiO 2, tidal volume (VT), positive end-expiratory pressure (PEEP) and other related factors which would change the correlation between SpO 2/FiO 2 and PaO 2/FiO 2. The receiver operator characteristic curve (ROC curve) was plotted to calculate the sensitivity and specificity of using SpO 2/FiO 2 instead of PaO 2/FiO 2 to assess oxygenation of ARDS patients. Results:Group 1 consisted of 24 ARDS patients from whom 271 blood gas analysis results were collected; group 2 consisted of 14 ARDS patients from whom a total of 47 blood gas analysis results were collected; group 3 consisted of 76 ARDS patients, and a total of 76 blood gas analysis results were collected. The PaO 2/FiO 2 (mmHg, 1 mmHg = 0.133 kPa) in groups 1, 2 and 3 were 103 (79, 130), 168 (98, 195) and 232 (146, 271) respectively, while SpO 2/FiO 2 were 157 (128, 190), 419 (190, 445) and 319 (228, 446) respectively. Among the three groups, patients in group 1 had the lowest PaO 2/FiO 2 and SpO 2/FiO 2, while patients in group 3 had the highest. Spearman correlation analysis showed that PaO 2/FiO 2 was highly correlated with SpO 2/FiO 2 in groups 1, 2 and 3 ( r values were 0.830, 0.951, 0.828, all P < 0.05). Regression equation was fitted according to linear analysis: in group 1 SpO 2/FiO 2 = 58+0.97×PaO 2/FiO 2 ( R2 = 0.548, P < 0.001) ; in group 2 SpO 2/FiO 2 = 6+2.13×PaO 2/FiO 2 ( R2 = 0.938, P < 0.001); in group 3 SpO 2/FiO 2 = 53+1.33×PaO 2/FiO 2 ( R2 = 0.828, P < 0.001). Further analysis revealed that PEEP, FiO 2, and arterial blood pH could affect the correlation between SpO 2/FiO 2 and PaO 2/FiO 2. ROC curve analysis showed that the area under ROC curve (AUC) was 0.848 and 0.916 in group 1 with moderate to severe ARDS; based on the regression equation, the corresponding SpO 2/FiO 2 cut-off values at a PaO 2/FiO 2 of 100 mmHg and 200 mmHg were 155, 252 with a sensitivity of 84.9% and 100%, specificity of 87.2% and 70.6%, respectively. Patients with moderate to severe ARDS in group 2 (AUC was 0.945 and 0.977), the corresponding SpO 2/FiO 2 cut-off values at PaO 2/FiO 2 of 100 mmHg and 200 mmHg were 219 and 432 with the sensitivity of 100% and 85.2%, specificity of 82.5% and 100%, respectively. Patients with mild to moderate-severe ARDS in group 3 (AUC was 0.903 and 0.936), the corresponding SpO 2/FiO 2 cut-off values at a PaO 2/FiO 2 of 200 mmHg and 300 mmHg were 319 and 452 with the sensitivity of 100% and 100%, specificity of 80.9% and 86.2%, respectively. Conclusion:SpO 2/FiO 2 and PaO 2/FiO 2 in ARDS patients at different high altitudes in Yunnan Province have a good correlation, and non-invasive SpO 2/FiO 2 can be used to replace PaO 2/FiO 2 to assess the oxygenation in ARDS patients.